A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024)

NCT05468697 | Active Not Recruiting Phase 1 FDA Drug

• 5 other identifiers: 6482-024MK-6482-024LITESPARK-0242023-504963-17-00U1111-1290-4845
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 13

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of belzutifan monotherapy and belzutifan plus palbociclib combination therapy in participants with advanced clear-cell renal cell carcinoma (ccRCC) who experienced disease progression on or after receiving prior therapy. The study will establish the safety of belzutifan plus palbociclib and determine a recommended dosage of palbociclib for the combination therapy by ascending dose escalation.

Conditions

Renal Cell Carcinoma

Keywords

Programmed cell death ligand 1 (PD-L1); Hypoxia inducible factor 2 alpha (HIF-2 alpha); Hypoxia inducible factor 2α (HIF-2α); Renal Cell Carcinoma (RCC); Kidney Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

  A DLT consists of one or more of the following toxicities: Grade (Gr) 3 or 4 hypoxia or dyspnea; Gr 3 or 4 nausea, vomiting, or diarrhea if persistent for \>48 hours despite therapy; Gr 3 or 4 cardiovascular, vascular, or thrombotic events; Nonhematologic AE ≥Gr 3 in severity with exceptions; Gr 3 rash that does not resolve within 2 weeks; Gr 3 nonhematologic toxicity if persisting despite optimal medical treatment; Gr 3 or 4 hematologic toxicities; Gr 3 or 4 febrile neutropenia; Gr 3 or 4 nonhematologic laboratory value; Any aspartate aminotransferase or alanine aminotransferase \>8x the upper limit of normal (ULN) or 5 to 8x ULN persisting for \>2 weeks; \>2 weeks delay in dosing due to intervention-related toxicity; Intervention-related toxicity causing intervention discontinuation in the first 28 days of dosing; Missing \>20% of intervention doses due to drug-related AEs; Gr 5 toxicity. The number of participants who experience at least one DLT will be reported.

  Up to approximately 28 days

• Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported.

  Up to approximately 4 years

• Number of Participants Who Discontinue Study Treatment Due to an AE

  An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. The number of participants who discontinued from the study treatment due to an AE will be reported.

  Up to approximately 4 years

Study Arms (3)

Beltuzifan 120 mg + Palbociclib 75 mg

EXPERIMENTAL

Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.

Drug: Belzutifan; Drug: Palbociclib

Beltuzifan 120 mg + Palbociclib 100 mg

EXPERIMENTAL

Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.

Drug: Belzutifan; Drug: Palbociclib

Beltuzifan 120 mg + Palbociclib 125 mg

EXPERIMENTAL

Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.

Drug: Belzutifan; Drug: Palbociclib

Interventions

Belzutifan DRUG

40 mg tablet administered orally at a dose of 120 mg.

Also known as: WELIREG™, MK-6482, PT2977

Beltuzifan 120 mg + Palbociclib 100 mg; Beltuzifan 120 mg + Palbociclib 125 mg; Beltuzifan 120 mg + Palbociclib 75 mg

Palbociclib DRUG

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

Also known as: IBRANCE®, PD 0332991

Beltuzifan 120 mg + Palbociclib 100 mg; Beltuzifan 120 mg + Palbociclib 125 mg; Beltuzifan 120 mg + Palbociclib 75 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer \[AJCC\], 8th Edition) RCC with clear-cell component
• Has had disease progression on or after having received at least 2 systemic treatments for unresectable Stage IV RCC with prior anti-programmed cell death 1 ligand 1 (PD-1/L1) and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
• Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR)
• Has recovered from all AEs due to previous therapies

You may not qualify if:

• Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has clinically significant cardiac disease
• Has moderate to severe hepatic impairment
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
• Has received prior treatment of belzutifan or palbociclib
• Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
• Has had major surgery ≤3 weeks prior to first dose of study intervention
• Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], or recombinant erythropoietin \[EPO\]) ≤28 days prior to the first dose of study intervention

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (13)

Georgetown University Medical Center ( Site 1002)

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Medical Center ( Site 1007)

Chicago, Illinois, 60637, United States

Location

Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)

Boston, Massachusetts, 02215, United States

Location

Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)

Salt Lake City, Utah, 84112, United States

Location

Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)

Macquarie University, New South Wales, 2109, Australia

Location

Westmead Hospital ( Site 2006)

Westmead, New South Wales, 2145, Australia

Location

Frankston Hospital-Oncology and Haematology ( Site 2005)

Frankston, Victoria, 3199, Australia

Location

One Clinical Research ( Site 2008)

Nedlands, Western Australia, 6009, Australia

Location

Emek Medical Center-oncology ( Site 3003)

Afula, 1834111, Israel

Location

Rambam Health Care Campus-Oncology ( Site 3000)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center-Oncology ( Site 3002)

Jerusalem, 9103102, Israel

Location

Rabin Medical Center-Oncology ( Site 3004)

Petah Tikva, 4941492, Israel

Location

Sourasky Medical Center ( Site 3005)

Tel Aviv, 6423906, Israel

Location

Related Publications (1)

• Meiman D, Skaar TC, Shugg T, Quinney SK. Physiologically Based Pharmacokinetic Model to Assess the Drug-Drug-Gene Interaction Potential of Belzutifan in Combination With Cyclin-Dependent Kinase 4/6 Inhibitors. JCO Precis Oncol. 2025 Jul;9:e2500153. doi: 10.1200/PO-25-00153. Epub 2025 Jul 25.

  PMID: 40712111 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

belzutifan; palbociclib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 21, 2022
• Study Start: August 10, 2022
• Primary Completion (Estimated): July 21, 2026
• Study Completion (Estimated): July 21, 2026
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); IL (5); US (4)